A Phase 2, Open-label, Multicenter, Safety and Efficacy Study of Oral Lucitanib in Patients With FGF Aberrant Metastatic Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 178
- 试验地点
- 33
- 主要终点
- Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by the Investigator
研究概览
简要总结
The purpose of this study is to determine whether lucitanib is safe and effective in the treatment of patients with FGF aberrant metastatic breast cancer, as well as in the treatment of patients with biomarker negative (FGF non-aberrant) metastatic breast cancer.
详细描述
Lucitanib is a selective, orally available tyrosine kinase inhibitor targeting FGFR1-3, VEGFR1-3, and PDGFRα and β, with activity in relevant cell lines and animal models.
The first in human trial of lucitanib demonstrated that daily dosing with lucitanib can provide durable clinical responses in patients with FGFR1- or 11q (FGF3, FGF4, Cyclin D1, or FGF19)-amplified breast cancer. RECIST partial responses (PRs) were also observed in patients not known to have FGF abnormalities.
Based on these results, this study is designed to explore the safety and anti-tumor activity of daily lucitanib in breast cancer patients with and without alterations of the FGF pathway.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed metastatic breast cancer relapsed or refractory to approved standard available treatment
- •Prior treatment with standard first line therapy in the metastatic setting
- •Availability of tumor tissue sufficient for confirmatory testing of FGFR1 and 11q amplification status
- •Demonstrated progression of disease by radiological or clinical assessment (Measurable disease according to RECIST Version 1.1 is NOT required for enrollment)
- •Estimated life expectancy >6 months
排除标准
- •Current or recent treatment with biologic anticancer therapies
- •Ongoing AEs from prior anticancer therapies
- •Active central nervous system (CNS) metastases
- •Clinically significant or uncontrolled hypertension or cardiac disease
- •Females who are pregnant or breastfeeding
研究组 & 干预措施
Cohort A: Lucitanib (CO-3810) 10 mg daily
10 mg of lucitanib daily in patients with FGFR1-amplified or 11q-amplified metastatic breast cancer.
干预措施: Lucitanib (Drug)
Cohort B: Lucitanib (CO-3810) 15 mg daily
15 mg of lucitanib daily in patients with FGFR1-amplified and 11q-amplified metastatic breast cancer.
干预措施: Lucitanib (Drug)
Cohort C: Lucitanib (CO-3810) 10 mg daily
10 mg of lucitanib daily in patients with FGFR1 non-amplified and 11q non-amplified metastatic breast cancer.
干预措施: Lucitanib (Drug)
结局指标
主要结局
Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by the Investigator
时间窗: From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months
The primary efficacy endpoint of PFS was calculated as 1+ the number of days from the date of first dose of study drug to disease progression or death due to any cause, whichever occurs first. Patients without a documented event of progression were censored on the date of their last adequate tumor assessment (i.e., radiologic assessment), or the date of randomization if no tumor assessments were performed. Progression events were determined by the investigator. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
次要结局
- Duration of Response (DR) by RECIST v1.1(From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months)
- Objective Response Rate (ORR) by RECIST v1.1(From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months)
- Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Total Score(From Cycle 1 Day 1 until end of treatment, assessed up to 29 months)
- Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - Cmax(Study Day -7 to Study Day 1, or approximately 8 days)
- Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - Tmax(Study Day -7 to Study Day 1, or approximately 8 days)
- Disease Control Rate (DCR) by RECIST v1.1(From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months)
- Overall Survival(Cycle 1 Day 1 to date of death, assessed up to 29 months)
- Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - AUClast(Study Day -7 to Study Day 1, or approximately 8 days)
- Relative Bioavailability Analysis for Tablet vs Capsule - Cmax, AUClast, AUCinf(Study Day -7 to Study Day 1, or approximately 8 days)
- Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - AUCinf(Study Day -7 to Study Day 1, or approximately 8 days)